The Study On The Antimyocardial Ischemia Effects And Mechanisms Of Rhodiola Freeze-dried Powder For Injection In Canines

Ischemic heart disease(IHD) is a main cause leading death. In order to develop new effective drugs against IHD,it is of great significance to find the active substances from the natural plants. Rhodiola from Rhodiola L(Genus) , Crassulaceae(Family) is perennial herbaceous or subbush plant. Rhodiola contains many effective elements, such as rhodioside and superoxide dismutase.Rhodiola is a traditional chinese medicine and has been used for a long history. Rhodiola has been proved to have many pharmacologial effects. Rhodiola has effects on nerve system,digestive system and cardiova scular.To investigate effects of rhodiola on the cardiovascular system and its mechanisms against ischemia, the acute myocardial ischemia model was made by ligating the left-decendent coronary artery in dogs. The square of myocardiac infarction , myocardial enzymology ,the degree and score of ischemia and hemodynamics were observed.Twenty-four dogs were randomly divided into four groups(n=6): control(saline) group, SHUXUENING 0.15mg.kg-1 group and rhodiola freeze-dried powder for injection 2.5mg·kg-1 ,5.0mg·kg-1 group. All drugs were administrated by intravenous drop infusion.Dogs were anesthetized with sodium pentobarbital 0.03g·kg-1adminstrated intravenously.Then trachea cannula, right common carotid artery cannula, right femoral vein cannula and left ventricle cannula were made in order. However, heart was exposed and left anterior descending coronary artery was isolated. Systolic blood pressure (SBP), diastolic blood pressure(DBP), cardiac output(CO), coronary blood flow (CBF), left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP), maximum left ventricular rise rate and maximum left ventricular fall rate(±dp/dtmax) were measured by RM-6000 physical recorder and MFV-3200 electromagnetic flow meter. ECG of standardⅡ, epicardium electrocardiogram(EECG)and heart rate were recorded at the same time.The stroke volume(SV),cardiac index(CI), stroke index(SI), left ventricular work index(LVWI), myocardial blood flow(MBF), coronary vascular resistance(CVR),myocardial oxygen consumption volume, myocardial oxygen consumption and total peripheral resistance (TPR) were calculated from above hemodynamic data.HR, MBP, LVSP, LVEDP,±dp/dtmax ,CO and CBF were recorded at 15,20,30,45,60,90,120,150,180,240 minutes after the drug was adminstrated and MAP,CI, SI ,LVWI and cardiac oxygen intake ratio, cardiac blood flow were calculated according to fomula.Blood was sampled at 360 min after the TSP administration. Serum was separated from blood cell, then lactate dehydrogenase (LDH), aminotransferase(AST),creatine kinase(CK), superoxide dismutase( SOD),malonyl dialdehyde(MAD) were determined at the end of each experiment.The heart was removed and cut into coronal sections and immersed in N-BT solution at 37°C. The percentage ratio of the weight of infracted necrotic myocardium to that of total ischemic myocardium was calculated and designated as the infarct size (%). The heart was examined by transmission electron microscope.1.The results showed that rhodiola freeze-dried powder for injection can decrease myocardial infarction size.2.Rhodiola freeze-dried powder for injection can decrease activity of AST, CK, LDH in serum and the level MDA in serum, improve SOD activity and ameliorate damage induced by free radicals. So rhodiola freeze-dried powder for injection can protect myocardium from ischemic injury.3.Rhodiola freeze-dried powder for injection can decrease the degree and score of myocardial.4.Rhodiola freeze-dried powder for injection had no effects on HR, MBP, LVSP LVEDP,±dp/dt. However, it can decrease the coronary resistance, increase cardiac blood flow, cardiac output, cardiac index, cardiac pumping index and cardiac pumping volume significantly. So Rhodiola freeze-dried powder for injection improved cardiac hemodynamics, decreased the oxygen consumption and maintained the balance between oxygen supply and demand in myocyte.5. Rhodiola freeze-dried powder for injection can ameliorate the injury induced by ischemia in myocardial ultrastracture bytransmission electromicroscopy.The results showed that rhodiola freeze-dried powder for injection has the protective effect on myocardial cell from injury induced by ischemia. The mechanisms involved that rhodiola freeze-dried power for injection have effects on hemodynamics, balancing need and providing of myocardium for oxygen, moderating myocardium injure and improving myocardiac metabolism. The study has been concluded that the results established solid foundation for clinical application of its effects on IHD .